Comparison of the efficacy and safety of fruquintinib and regorafenib in the treatment of metastatic colorectal cancer: A real-world study.

Background: Fruquintinib and regorafenib have been approved for the third-line therapy of metastatic colorectal cancer (mCRC) in China. However, at present, there is a lack of head-to-head clinical trials on the comparison of efficacy and safety between the two drugs. Materials and methods: The data of patients with mCRC who were treated with fruquintinib or regorafenib after the standard chemotherapy in Zhejiang Provincial People's Hospital from October 2018 to November 2021 were collected and analyzed. The primary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. The secondary endpoints were the appropriate sequence, objective remission rate (ORR) and disease control rate (DCR) of fruquintinib and regorafenib. Results: A total of 105 patients were enrolled in this study. The ORR of fruquintinib group (n=55) and regorafenib group (n=50) were 6.1% and 2.0%; the DCR were 65.3% and 54.2%, respectively. There was no significant difference in median OS (mOS) and PFS (mPFS) between the two groups (mOS:14.2 vs12.0 months, p=0.057; mPFS:4.4 vs 3.5 months, p=0.150). Combined immunotherapy showed a synergistic effect. The mPFS and mOS of fruquintinib combined with anti-PD-1 therapy were longer than those of fruquintinib monotherapy (mPFS:5.9 vs 3.0 months, p=0.009; mOS:17.5 vs 11.3 months, p=0.008). The mOS of patients treated with regorafenib combined with anti-PD-1 therapy was 14.8 months higher than that of regorafenib monotherapy (p=0.045). When combined with anti-PD-1 therapy, the mPFS and mOS of fruquintinib was significantly longer than regorafenib (mPFS:5.9 vs 3.8 months, p=0.018; mOS:17.5 vs 14.8 months, p=0.044). In the treatment sequence, the OS of patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence (15.0 vs 8.3 months, p=0.019). The adverse reactions were generally similar, but the incidence of hand-foot syndrome of regorafenib was higher than that of fruquintinib, while fruquintinib was more prone to grade 3 hypertension. Conclusion: Fruquintinib monotherapy showed better disease control rate and objective remission rate in the post-line therapy of metastasis colorectal cancer. Notably, the combination of PD-1 immunotherapy brought the additional effect, especially in the fruquintinib combined with anti-PD-1 therapy. Patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence. The toxicity of fruquintinib and regorafenib are similar.

The D-amino acid oxidase inhibitor luvadaxistat improves mismatch negativity in patients with schizophrenia in a randomized trial.

Several attempts have been made to enhance N-methyl-D-aspartate (NMDA) receptor function in schizophrenia, but they have yielded mixed results. Luvadaxistat, a D-amino acid oxidase (DAAO) inhibitor that increases the glutamate co-agonist D-serine levels, is being developed for the treatment of cognitive impairment associated with schizophrenia. We conducted a biomarker study in patients, assessing several endpoints related to physiological outcomes of NMDA receptor modulation to determine whether luvadaxistat affects neural circuitry biomarkers relevant to NMDA receptor function and schizophrenia. This was a randomized, placebo-controlled, double-blind, two-period crossover phase 2a study assessing luvadaxistat 50 mg and 500 mg for 8 days in 31 patients with schizophrenia. There were no treatment effects of luvadaxistat at either dose in eyeblink conditioning, a cerebellar-dependent learning measure, compared with placebo. We observed a nominally significant improvement in mismatch negativity (MMN) and a statistical trend to improvement for auditory steady-state response at 40 Hz, in both cases with 50 mg, but not with 500 mg, compared with placebo. Although the data should be interpreted cautiously owing to the small sample size, they suggest that luvadaxistat can improve an illness-related circuitry biomarker at doses associated with partial DAAO inhibition. These results are consistent with 50 mg, but not higher doses, showing a signal of efficacy in cognitive endpoints in a larger phase 2, 12-week study conducted in parallel. Thus, MMN responses after a short treatment period may predict cognitive function improvement. MMN and ASSR should be considered as biomarkers in early trials addressing NMDA receptor hypofunction.

Understanding the Effect of Top Electrode on Ferroelectricity in Atomic Layer Deposited Hf0.5Zr0.5O2 Thin Films.

It is commonly believed that the impact of the top electrodes on the ferroelectricity of hafnium-based thin films is due to strain engineering. However, several anomalies have occurred that put existing theories in doubt. This work carries out a detailed study of this issue using both theoretical and experimental approaches. The 10 nm Hf0.5Zr0.5O2 (HZO) films are prepared by atomic layer deposition, and three different top capping electrodes (W/MO/ITO) are deposited by physical vapor deposition. The electrical testing finds that the strain does not completely control the ferroelectricity of the devices. The results of further piezoelectric force microscopy characterization exclude the potential interference of the top capping electrodes and interface for electrical testing. In addition, through atomic force microscopy characterization and statistical analysis, a strong correlation between the grain size of the top electrode and the grain size of the HZO film has been found, suggesting that the grain size of the top electrode can induce the formation of the grain size in HZO thin films. Finally, the first-principles calculation is carried out to understand the impact of the strain and grain size on the ferroelectric properties of HZO films. The results show that the strain is the dominant factor for ferroelectricity when the grain size is large (>10 nm). However, when the grain size becomes thinner (<10 nm), the regulation effect of grain sizes increases significantly, which could bring a series of benefits for device scaling, such as device-to-device variations, film uniformity, and domain switch consistency. This work not only completes the understanding of ferroelectricity through top electrode modulation but also provides strong support for the precise regulation of ferroelectricity of nanoscale devices and ultrathin HZO ferroelectric films.

The association of birthweight with fine particle exposure is modifiable by source sector: Findings from a cross-sectional study of 17 low- and middle-income countries.

BACKGROUND: Low birthweight attributable to fine particulate matter (PM2.5) exposure is a global issue affecting infant health, especially in low- and middle-income countries (LMICs). However, large-population studies of multiple LMICs are lacking, and little is known about whether the source of PM2.5 is a determinant of the toxic effect on birthweight. OBJECTIVE: We examined the effect on birthweight of long-term exposure to PM2.5 from different sources in LMICs. METHODS: The birthweights of 53,449 infants born between September 16, 2017 and September 15, 2018 in 17 LMICs were collected from demographic and health surveys. Long-term exposure to PM2.5 in 2017 produced by 20 different sources was estimated by combining chemical transport model simulations with satellite-based concentrations of total mass. Generalized linear regression models were used to investigate the associations between birthweight and each source-specific PM2.5 exposure. A multiple-pollutant model with a ridge penalty on the coefficients of all 20-source-specific components was employed to develop a joint exposure-response function (JERF) of the PM2.5 mixtures. The estimated JERF was then used to quantify the global burden of birthweight reduction attributable to PM2.5 mixtures and to PM2.5 from specific sources. RESULTS: The fully adjusted single-pollutant model indicated that exposure to a 10 µg/m3 increase in total PM2.5 was significantly associated with a -6.6 g (95% CI -11.0 to -2.3) reduction in birthweight. In single- and multiple-pollutant models, significant birthweight changes were associated with exposure to PM2.5 produced by international shipping (SHP), solvents (SLV), agricultural waste burning (GFEDagburn), road transportation (ROAD), waste handling and disposal (WST), and windblown dust (WDUST). Based on the global average exposure to PM2.5 mixtures, the JERF showed that the overall change in birthweight could mostly be attributed to PM2.5 produced by ROAD (-37.7 g [95% CI -49.2 to -24.4] for a global average exposure of 2.2 µg/m3), followed by WST (-27.5 g [95% CI -42.6 to -10.7] for a 1.6-µg/m3 exposure), WDUST (-19.5 g [95% CI -26.7 to -12.6] for a 8.6-µg/m3 exposure), and SHP (-19.0 g [95% CI -32.3 to -5.7] for a 0.2-µg/m3 exposure), which, with the exception of WDUST, are anthropogenic sources. The changes in birthweight varied geographically and were co-determined by the concentration as well as the source profile of the PM2.5 mixture. CONCLUSION: PM2.5 exposure is associated with a reduction in birthweight, but our study shows that the magnitude of the association differs depending on the PM2.5 source. A source-targeted emission-control strategy that considers local features is therefore critical to maximize the health benefits of air quality improvement, especially with respect to promoting maternal and child health.

The sex pheromone heptacosane enhances the mating competitiveness of sterile Aedes aegypti males.

BACKGROUND: Aedes aegypti is a vector that transmits various viral diseases, including dengue and Zika. The radiation-based sterile insect technique (SIT) has a limited effect on mosquito control because of the difficulty in irradiating males without reducing their mating competitiveness. In this study, the insect sex pheromone heptacosane was applied to Ae. aegypti males to investigate whether it could enhance the mating competitiveness of irradiated males. METHODS: Heptacosane was smeared on the abdomens of Ae. aegypti males that were allowed to mate with untreated virgin females. The insemination rate was used to assess the attractiveness of heptacosane-treated males to females. The pupae were irradiated with different doses of X-rays and γ-rays, and the emergence, survival time, egg number, and hatch rate were detected to find the optimal dose of X-ray and γ-ray radiation. The males irradiated at the optimal dose were smeared with heptacosane, released in different ratios with untreated males, and mated with females. The effect of heptacosane on the mating competitiveness of irradiated mosquitoes was then evaluated by the hatch rate, induced sterility, and mating competitiveness index. RESULTS: Applying heptacosane to Ae. aegypti males significantly increased the insemination rate of females by 20%. Pupal radiation did not affect egg number but significantly reduced survival time and hatch rate. The emergence of the pupae was not affected by X-ray radiation but was affected by γ-ray radiation. Pupae exposed to 60 Gy X-rays and 40 Gy γ-rays were selected for subsequent experiments. After 60 Gy X-ray irradiation or 40 Gy γ-ray irradiation, the average hatch rate was less than 0.1%, and the average survival time was more than 15 days. Moreover, at the same release ratio, the hatch rate of the irradiated group perfumed with heptacosane was lower than that of the group without heptacosane. Conversely, the male sterility and male mating competitiveness index were significantly increased due to the use of heptacosane. CONCLUSIONS: The sex pheromone heptacosane enhanced the interaction between Ae. aegypti males and females. Perfuming males irradiated by X-rays or γ-rays with heptacosane led to a significant increase in mating competitiveness. This study provided a new idea for improving the application effect of SIT.

Influence of artificial intelligence in education on adolescents' social adaptability: The mediatory role of social support.

Artificial intelligence (AI) is widely used in the field of education at present, but people know little about its possible impacts, especially on the physical and mental development of the educated. It is important to explore the possible impacts of the application of artificial intelligence in education (AIEd) in order to avoid the possible adverse effects. Prior research has focused on theory to the exclusion of the psychological impact of AIEd, and the empirical research was relatively lacking. This study aimed to identify the influence of AIEd on adolescents' social adaptability via social support. A total of 1332 students were recruited using random sampling from 13 Artificial Intelligence Curriculum Reform Experimental Schools in Guangzhou, Southern China, completed the survey. There were 342 primary school students (Meanage = 10.6), 351 junior high school students (Meanage = 13.1), and 639 senior high school students (Meanage = 15.8). Results showed that AIEd has a negative impact on adolescents' social adaptability, and is significantly negatively correlated with social adaptability and family support, but there is no significant correlation with school support. AIEd could not only affect social adaptability directly, but also could affected it through the family support.

Repeatability of metabolic tumor burden and lesion glycolysis between clinical readers.

The Metabolic Tumor Volume (MTV) and Tumor Lesion Glycolysis (TLG) has been shown to be independent prognostic predictors for clinical outcome in Diffuse Large B-cell Lymphoma (DLBCL). However, definitions of these measurements have not been standardized, leading to many sources of variation, operator evaluation continues to be one major source. In this study, we propose a reader reproducibility study to evaluate computation of TMV (& TLG) metrics based on differences in lesion delineation. In the first approach, reader manually corrected regional boundaries after automated detection performed across the lesions in a body scan (Reader M using a manual process, or manual). The other reader used a semi-automated method of lesion identification, without any boundary modification (Reader A using a semi- automated process, or auto). Parameters for active lesion were kept the same, derived from standard uptake values (SUVs) over a 41% threshold. We systematically contrasted MTV & TLG differences between expert readers (Reader M & A). We find that MTVs computed by Readers M and A were both concordant between them (concordant correlation coefficient of 0.96) and independently prognostic with a P-value of 0.0001 and 0.0002 respectively for overall survival after treatment. Additionally, we find TLG for these reader approaches showed concordance (CCC of 0.96) and was prognostic for over -all survival (p ≤ 0.0001 for both). In conclusion, the semi-automated approach (Reader A) provides acceptable quantification & prognosis of tumor burden (MTV) and TLG in comparison to expert reader assisted measurement (Reader M) on PET/CT scans.

Investigations into the impact of non-coding RNA on the sensitivity of gastric cancer to radiotherapy.

Non-coding RNAs (ncRNAs) are a newly discovered functional RNA different from messenger RNA, which can participate in regulating the occurrence and development of tumors. More and more research results show that ncRNAs can participate in the regulation of gastric cancer (GC) radiotherapy response, and its mechanism may be related to its effect on DNA damage repair, gastric cancer cell stemness, cell apoptosis, activation of epidermal growth factor receptor signaling pathway, etc. This article summarizes the relevant mechanisms of ncRNAs regulating the response to radiotherapy in gastric cancer, which will be directly important for the introduction of ncRNAs particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) into clinical medicine as biomarkers and therapeutic targets.

Vincristine and dexamethasone pulses in addition to maintenance therapy among pediatric acute lymphoblastic leukemia (GD-ALL-2008): An open-label, multicentre, randomized, phase III clinical trial.

The efficacy and safety on the addition of vincristine (VCR) and dexamethasone (DEX) pulses to maintenance therapy among childhood acute lymphoblastic leukemia (ALL) remain uncertain. Herein, we perform an open-label, multicentre, randomized, phase III clinical trial that was conducted at nine major medical centers in Guangdong Province, China. Patients were randomly assigned either the conventional maintenance therapy (control group, n = 384) or the VCR/DEX pulse (treatment group, n = 375). When limited to the SR cohort, 10-year EFS was 82.6% (95% CI: 75.9-89.9) in the control group and 80.7% (95% CI: 74-88.1) in the treatment group (pnon-inferiority  = .0002). Similarly, patients with IR also demonstrated non-inferiority of the treatment group to the control group in terms of 10-year EFS (73.6% [95% CI: 67.6-80] vs. 77.6% [95% CI: 71.8-83.9]; pnon-inferiority  = .005). Among the HR cohort, compared with the control group, patients in the treatment group experienced a significant benefit in terms of 10-year EFS (61.1% [95% CI: 47.7-78.2] vs. 72.6% [95% CI: 55.6-94.7], p = .026) and a trend toward higher 10-year OS (73.8% [95% CI: 61.6-88.4] vs. 87.9% [95% CI: 579.2-97.5], p = .068). In the HR cohort, the total rate of drug-induced liver injury and Grade 3 chemotherapy-induced anemia were both lower for patients in the treatment group than in the control group (55.6% vs. 100%, p = .033; 37.5% vs. 60%, p = .036). Conversely, the total prevalence of chemotherapy-induced thrombocytopenia was higher for patients in the treatment group than in the control group (88.9% vs. 40%, p = .027). Pediatric acute lymphoblastic leukemia with high risk is suitable to VCR/DEX pulse during maintenance phase for the excellent outcome, while the standard-to-intermediate-risk patients could eliminate the pulses.

The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage.

Background: Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia. Methods: Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman's analysis. Results: A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman's analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147). Conclusions: Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.

Performance evaluation of a novel 14C-urea breath test (solid scintillation) for the diagnosis of helicobacter pylori infection.

14C-urea breath tests (UBTs) can be used to diagnose helicobacter pylori (H. pylori) infection. This study aimed to evaluate the accuracy of a solid scintillation 14C-UBT in diagnosing H pylori infection. This open-label, prospective multicenter study enrolled patients who underwent H pylori screening from January 7, 2020, to October 28, 2020, in 3 centers in China. All participants underwent solid scintillation UBT first and then gastroscopy. The rapid urease test and histological examination results were the gold standards (H pylori-positive was defined as the 2 tests being positive; H pylori-negative was defined as both tests being negative). The solid scintillation 14C-UBT involves a scintillation sampling bottle and a 14C-urea capsule. The sampling bottle contains a stack of carbon dioxide-absorbing and scintillation sheets. The test is read using a photomultiplier. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for H pylori infection were evaluated. This study enrolled 239 participants. There were 98 males and 141 females, aged 45.8 ±â€…11.9 (range: 21-66) years. Thirty-four participants were excluded due to a discrepancy between the rapid urease test and immunohistochemistry examination. Finally, 205 participants were included in the analysis. According to the gold standard, 87 out of 205 (42.4%) participants were H pylori-positive. Compared with the gold standard, the sensitivity, specificity, accuracy, and positive and negative predictive values of the solid scintillation 14C-UBT were 95.4%, 97.5%, 96.6%, 96.5%, and 96.6% for the solid scintillation UBT, respectively. One participant experienced 1 adverse event (AE) (exacerbation of chronic cholecystitis), and the AE eventually improved by itself. The investigators determined that the AE was unrelated to the study device. The noninvasive solid scintillation 14C-UBT has a high diagnostic value for H pylori infection, comparable to the diagnostic value of the gold standard.

The mechanism and therapy of aortic aneurysms.

Aortic aneurysm is a chronic aortic disease affected by many factors. Although it is generally asymptomatic, it poses a significant threat to human life due to a high risk of rupture. Because of its strong concealment, it is difficult to diagnose the disease in the early stage. At present, there are no effective drugs for the treatment of aneurysms. Surgical intervention and endovascular treatment are the only therapies. Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm, the specific mechanisms remain unclear. Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment. To better understand aortic aneurysm, this review elaborates on the discovery history of aortic aneurysm, main classification and clinical manifestations, related molecular mechanisms, clinical cohort studies and animal models, with the ultimate goal of providing insights into the treatment of this devastating disease. The underlying problem with aneurysm disease is weakening of the aortic wall, leading to progressive dilation. If not treated in time, the aortic aneurysm eventually ruptures. An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall. The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.

Effect of riboflavin and carbon black co-modified fillers coupled with alkaline pretreatment on anaerobic digestion of waste activated sludge.

Additional various carbon and free riboflavin could improve anaerobic digestion of waste activated sludge (WAS). However, these substances were not reused. In this study, a reusable riboflavin and carbon black (RCB) co-modified filler was developed and combined with alkaline pretreatment for enhancing the production of volatile fatty acids (VFAs) and methane during anaerobic digestion of WAS. The results showed that RCB-modified fillers exhibited a promoting effect on the reduction of alkali-pretreated WAS. The amounts of the accumulated VFAs mainly containing acetate and the produced methane rose with the increased concentration of immobilized riboflavin (0-0.75 g/L) in the presence of 4 g/L carbon black. When the alkaline pretreatment time of WAS increased from 3 d to 8 d, the amount of methane production increased from 22.8% to 63.9% in the presence of 0.75 g/L riboflavin and 4 g/L carbon black compared with that without RCB-modified fillers. Moreover, 0.75 g/L riboflavin and 4 g/L carbon black had a synergetic effect on promoting methane production via broadening extracellular electron transfer pathways. During this process, microbial dehydrogenase activity, electron transport system activity and coenzyme F420 were enhanced. Microbial community analysis showed that RCB-modified filler addition promoted the enrichment of Syntrophomonas and Pseudomonas involved in direct interspecies electron transfer (DIET). These results indicated that DIET establishment was accelerated. Meanwhile, the populations of acetic acid-producing bacteria including Rikenellaceae_RC9_gut_group and Proteiniphilum, aceticlastic and acid-tolerant methanogenic archaea including Methanosarcina and Methanosaeta, RumEn_M2 were increased. These results indicate that RCB-modified fillers coupled with alkaline pretreatment is an effective method to promote the production of methane during anaerobic digestion of WAS.

The epidemiology and healthcare costs of community-acquired pneumonia in Ontario, Canada: a population-based cohort study.

OBJECTIVES: The aim of the present study was to determine incidence-based short- and long-term healthcare costs attributable to community-acquired pneumonia (CAP) from the healthcare payer perspective in Ontario, Canada. METHODS: We conducted a retrospective population-based matched cohort study of residents in Ontario, Canada using health administrative data. We identified subjects with an incident episode of CAP (exposed subjects) between 1 January 2012 and 31 December 2014. The index date of each episode was based on the first inpatient or outpatient claim for pneumonia. Exposed subjects were matched without replacement to unexposed subjects from the general population using hard and propensity score matching on age, sex, income quintile, rural residence, comorbidities, and healthcare costs prior to index date. Attributable costs represented the mean difference in costs between the exposed subjects and their matched pairs. RESULTS: We identified 692,090 subjects with at least one episode of CAP between 1 January 2012 and 31 December 2014. Adults aged 65 years and older had the highest annual incidence rate of 50.1 episodes per 1,000 person-years, while adults aged 18-64 years and children (aged 0-17) had incidence rates of 12.9 and 24.7 episodes per 1,000 person-years, respectively. The majority of episodes involved care exclusively in the outpatient setting (92.6%), with most of these episodes involving a single physician visit. The mean attributable costs were $1,595 (95% CI: $1,572-$1,616) per outpatient CAP episode and $12,576 (95% CI: $12.392-$12,761) per inpatient CAP episode. Attributable costs were significantly higher for adult subjects and those with time spent in the intensive care unit. Alternative case definitions yielded different results, although demonstrated the same overall trends across groups. CONCLUSION: CAP is associated with substantially increased acute and long-term healthcare costs compared to unexposed subjects. This study highlights the burden of CAP in both the inpatient and outpatient setting, and will serve to inform strategic healthcare planning for future interventions and healthcare programs.

[Changes and significance of type 2 innate lymphoid cells and their related factors in bronchopulmonary dysplasia]. / 2åž‹å›ºæœ‰æ·‹å·´ç»†èƒžåŠå ¶ç›¸å ³å› å­åœ¨æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯ä¸­çš„å˜åŒ–åŠæ„ä¹‰.

OBJECTIVES: To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth. RESULTS: The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05). CONCLUSIONS: Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.

Chidamide as maintenance after chemotherapy or hematopoietic stem cell transplantation in 27 children with T-cell lymphoblastic leukemia: A real-world prospective study.

Background: The long-term overall survival of children with T-cell acute lymphoblastic leukemia (T-ALL) is limited to approximately 80-85% because of a high incidence of relapse after achieving remission with intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Novel treatment strategies inducing long-term remission are needed to improve the outcome. Histone deacetylase inhibitors (HDACis) have been reported to be effective in a series of T-ALL cases. Preclinical studies suggested that T-ALL cells are sensitive to Chidamide, which is a selective HDACi. Methods: This preliminary clinical study evaluated the efficacy and safety of Chidamide in combination with chemotherapy or post-HSCT for children with T-ALL at a dose of 0.5 mg/kg weight of patient twice per week for at least 6 months. Results: In total, 27 children with a mean age of 7.88 years were included. The high-risk proportion was 66.7%. After a median follow-up period of 37.8 months (9.5-67.9 months), the overall survival and event-free survival in the patients treated with Chidamide were 94.1 and 95.2%, respectively. All patients except two maintained persistent remission with <0.01% blast cells in minimal residual disease. Conclusion: The combination therapy with Chidamide in a case series of T-ALL shows the promising clinical efficacy and good safety in children. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2000030357.

Study on the mechanism of Phellinus igniarius total flavonoids in reducing uric acid and protecting uric acid renal injury in vitro.

Background: Uric acid nephropathy (UN) is a complication of hyperuricemia (HUA), which has a great impact on people's lives. Here, we evaluated the therapeutic potential of total flavonoids of Phellinus igniarius (TFPI) in vivo and studied the anti UN effect of TFPI in vitro. Methods: Hyperuricemia was induced by intraperitoneal injection of potassium oxonate in ICR mice. After intervention with TFPI, we evaluated the levels of serum uric acid (UA) and creatinine (CR), and the contents of xanthine oxidase (XOD) and adenosine deaminase (ADA) in liver. To explore the effect and molecular mechanism of TFPI on UN, we treated HK-2 cells with monosodium urate (MSU) to study the effect of TFPI on apoptosis and inflammation. In addition, to explore the mechanism of TFPI on uric acid transport we evaluated the relationship between uric acid transporter ABCG2 and inflammatory signaling pathway TLR4-NLRP3. Results: In the model mice, TFPI significantly decreased the levels of UA and Cr, which may be related to the inhibition of XOD enzyme activity. In HK-2 cells, the response of TFPI to MSU can effectively inhibit apoptosis and activation of TLR4-NLRP3 signaling pathway and promote the expression of ABCG2. Conclusions: TFPI can significantly inhibit the release of inflammatory factors and promote the expression of ABCG2 by targeting TLR4 receptor and NLRP3 inflammasome. And targeted inhibition of XOD enzyme activity to reduce uric acid level and inhibit the development of UN.